During organogenesis the proper spacial and temporal development of the vasculature is of fundamental importance to normal organ morphogenesis. During craniofacial ontogeny a temporal aberration in the development of the vasculature can causally be related to the etiology of cleft lip and palate, and Treacher's syndrome. During embryogenesis most tissues vascularize. There are, however, tissues or organs that do not vascularize. What is the contribution of the vasculature to organogenesis? What is the biochemical "information" that regulates which tissues or organs vascularize? The chick chorio-allantoic membrane grafting technique for explanting tissues, modified into a bioassay system, provides a means to study tissue and organ vascularization. Knowledge of when and where vascularization occurs will provide the basis for determination of the development of biochemical "information" responsible for the differentiation of vascularizing and non-vascularizing regions during organogenesis. Do non-vascularizing organs contain "information" that inhibits endothelium from invading the organ? Preliminary evidence indicated that cartilage contained such information in the form of a "protease inhibitor" and an additional inhibitor of endothelial cell proliferation. The isolation and purification of such factor(s) will provide a tool to study cell-cell interactions related to the development of the vasculature and organ formation. Such an approach is imperative in studies to prevent and understand craniofacial anomalies.